Anti-Retroviral (ARV) Drugs or

Anti-Retroviral (ARV) Drugs or Anti-Retroviral Therapy (ART)

Types of ARV drugs

There are three main types of ARV drugs:

Nucleoside analogue reverse transcriptase inhibitors (NRTIs)

Non-nucleoside reverse transcriptase inhibitors (NNRTIs).

Protease inhibitors (PIs)

NRTIs attack an HIV protein called reverse transcriptase. These were the first type of drugs available to treat HIV. Today, two NRTIs often form the backbone of any anti-HIV drug combination.

Examples of the Different Classes

Nucleoside analogue reverse transcriptase inhibitors - NRTIs

AZT, zidovudine (Retrovir) - Glaxo Smith Kline

ddI, didanosine, (Videx) - Bristol Myers Squibb

ddC, zalcitabine (Hivid) - Roche

3TC, lamivudine (Epivir) - Glaxo Smith Kline

d4T, stavudine (Zerit) - Bristol Myers Squibb

ABC, abacavir (Ziagen) - Glaxo Smith Kline

Non-nucleoside analogue reverse transcriptase inhibitors - NNRTIs

Nevirapine (Viramune)* - Boehringer Ingelheim

Efavirenz (Sustiva) - Merck

Delavirdine (Rescriptor) - Pharmacia and Upjohn

Protease Inhibitors - PIs

Indinavir (Crixivan) - Merck

Saquinavir (Fortovase) - Roche

Ritonavir (Norvir) - Abbott

Nelfinavir (Viracept) - Agouron in the U.S., Roche in the rest of the

world

Amprenavir (Agenerase) - Glaxo Smith Kline

Combined pill of ritonavir and lopinavir (Kaletra) - Abbott

Do you take more than one drug at the time?

You need to take at least two and preferably three drugs at the same time. The reason for this is that if you only take one drug, it will just be a short time before the drug will stop working. This is referred to as becoming "resistant" to the drug. If you take several drugs together, and if the drugs are from more than one group, then it generally takes longer before you become resistant.

How do you decide which drugs to take?

The decision about which drugs to take depends on a number of different factors. These include the availability and price of drugs, the numbers of pills, the side-effects of the drugs, the laboratory monitoring requirements and whether there are co-blister packs or fixed dose combinations available.

What are co-blister packs and fixed dose combinations (FDC)?

A co-blister pack is when two or more pills, capsules or tablets are packaged together in one unit in a plastic or aluminium blister pack. In contrast, a fixed dose combination (FDC) is when two or more drugs are combined together in one pill, capsule or tablet.

FDCs reduce the number of pills or tablets to be taken. Also the person taking the pills cannot leave out one of their drugs by not taking some of the pills. This improves the ability of people to take the drugs correctly (known as adherence) and it limits the emergence of resistance. Co-blister packs help people to take the pills at the correct time by packaging them together, but the drugs can still be separated, and co-blister packs do not reduce the number of pills or tablets to be taken.

What are recommended drug combinations by World Health organization (WHO)?

First line regimen

There is a need in any combination to have drugs from more than one group. And in general the drugs from the protease inhibitor (PI) group are the least suitable for a number of reasons including cost, the number of pills which need to be taken, and the particular side effects that occur with the protease drugs.

So WHO recommends that generally a first line regime should consist of two drugs from the nucleoside (NRTI) group and one from the non-nucleoside (NNRTI) group. More specifically they recommend just four possible combinations which are listed below.

WHO Recommendations for a First Line Regimen in Adults and Adolescents

Drugs to be taken	Use in Women of Childbearing age or who are Pregnant?	Available as FDC?
Stavudine + Lamivudine + Nevirapine *	Yes	Yes
Zidovudine + Lamivudine + Nevirapine*	Yes	Yes
Stavudine + Lamivudine + Efavirenz	No	No
Zidovudine + Lamivudine + Efavirenz	No	No

3TC is recommended for inclusion in all instances, because it is a potent drug, and WHO considers that it has an excellent record of efficacy, safety and tolerability. It can be taken either once or twice daily, and it has been incorporated into a number of fixed dose combinations.

With regard to making a choice between d4T and ZDV, d4T is initially better tolerated than ZDV but among the NRTIs, it has been most consistently associated with certain metabolic abnormalities, and it can also cause peripheral neuropathy and pancreatitis. ZDV can also cause metabolic abnormalities, but it would seem to a lesser extent. However, ZDV can cause severe anaemia and neutropenia, and this requires that haemoglobin is monitored both prior to and during treatment with ZDV.

NVP has a higher incidence of rash and a greater risk of hepatotoxicity (damage to the liver) both of which can be life threatening. This makes the drug less suitable for treating patients who may be on other hepatotoxic medications, or that can cause rash, such as rifampicin (used for TB treatment).